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Reciprocal modulation of I h and I TASK in thalamocortical relay neurons by halothane

  • Cellular Neurophysiology
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Abstract

By combining electrophysiological, immunohistochemical, and computer modeling techniques, we examined the effects of halothane on the standing outward current (I SO) and the hyperpolarization-activated current (I h) in rat thalamocortical relay (TC) neurons of the dorsal lateral geniculate nucleus (dLGN). Hyperpolarizing voltage steps elicited an instantaneous current component (I i) followed by a slower time-dependent current that represented I h. Halothane reduced I h by shifting the voltage dependency of activation toward more negative potentials and by reducing the maximal conductance. Moreover, halothane augmented I i and I SO. During the blockade of I h through Cs+, the current–voltage relationship of the halothane-sensitive current closely resembled the properties of a current through members of the TWIK-related acid-sensitive K+ (TASK) channel family (I TASK). Computer simulations in a single-compartment TC neuron model demonstrated that the modulation of I h and I TASK is sufficient to explain the halothane-induced hyperpolarization of the membrane potential observed in current clamp recordings. Immunohistochemical staining revealed protein expression of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel proteins HCN1, HCN2, and HCN4. Together with the dual effect of halothane on I h properties, these results suggest that I h in TC neurons critically depends on HCN1/HCN2 heterodimers. It is concluded that the reciprocal modulation of I h and I TASK is an important mechanism of halothane action in the thalamus.

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Acknowledgements

The authors wish to thank E. Naß and A. Jahn for the excellent technical assistance. We also wish to thank Prof. J. Andersson for his kind help with the gas chromatography and Prof. E. Pogatzki-Zahn for kindly providing the sevoflurane. This study was supported by DFG (BU 1019/7-1; Pa 336/17-1), Innovative Medizinische Forschung (IMF; BU 120501), and Interdisziplinäres Zentrum für Klinische Forschung (IZKF; Bud/005/07 to TB; A-54 to SGM).

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Authors and Affiliations

  1. Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Robert-Koch-Str. 27a, 48149, Münster, Germany

    Thomas Budde, Philippe Coulon, Matthias Pawlowski, Patrick Meuth, Tatyana Kanyshkova & Hans-Christian Pape

  2. Institut für Anorganische und Analytische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstr. 30/36, 48149, Münster, Germany

    Ansgar Japes

  3. Klinik für Neurologie, Julius-Maximilians-Universität Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany

    Sven G. Meuth

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  1. Thomas Budde
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Correspondence to Thomas Budde.

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Thomas Budde and Philippe Coulon are equally contributing first authors.

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Budde, T., Coulon, P., Pawlowski, M. et al. Reciprocal modulation of I h and I TASK in thalamocortical relay neurons by halothane. Pflugers Arch - Eur J Physiol 456, 1061–1073 (2008). https://doi.org/10.1007/s00424-008-0482-9

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